A surgical sealant or tissue adhesive (hereinafter collectively referred to as “sealant”) is a material, which is applied to an anastomosed part among tissues or a damaged portion of a living body to form a sealant membrane, thereby preventing leakage of blood or air. It is used in various surgeries, such as respiratory surgery, gastrointestinal surgery, cardiovascular surgery, oral surgery or the like. The most widely used sealant nowadays is a fibrin sealant (Bolheal® produced by Kaketsuken). The sealant has an excellent biocompatibility but has a problem of relatively low adhesion to the tissue and low sealing strength of an affected part. The sealing strength as used herein is measured as pressure-resistant strength or burst strength of the membrane, for which both strength of the membrane itself and adhesion strength of the membrane to living tissues are required.
To solve the aforesaid problem, the present inventor has been developing a sealant comprising a gelatin having a hydrophobic group, hereinafter may be referred to as “hydrophobically modified gelatin” (for example, Patent document 1, and Patent document 2). The membrane obtained from the sealant has a higher adhesion and sealing strengths and less swelled by body fluid.
However, in addition to the properties as mentioned above, it is important for a biological material to have the sterilization resistance in the form of a final product, that is, packed in a final container or package. The Japanese Pharmacopoeia specifies that a final sterilization method should be selected from thermal method, radiation method, and gaseous method (The Japanese Pharmacopoeia, Fourteenth Edition, Part II, the reference information, page 1235). The aforesaid fibrin sealant is sterilized by the thermal method, but it is not applicable to the hydrophobically modified gelatin because a molecular weight thereof is decreased by hydrolysis. The gaseous method is not applicable, either, because the hydrophobically modified gelatin is typically used in the form of an aqueous solution. Consequently, the radiation method is to be used, but it is very difficult to sterilize a material mainly composed of protein such as gelatin without denaturing.
For example, Patent document 3, which relates to a radiation sterilization of a collagen gel, describes that the radiation sterilization significantly impair properties of the collagen gel by causing a partial crosslinking and decomposition reactions (Patent document 3, paragraph [0005]) and proposes adding to the collagen gel a radiation protective agent, such as a heat-denatured atelocollagen. In addition, a method of irradiating a polymer such as gelatin by blending a polyfunctional triazine compound in the polymer (Patent Document 4)